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Identification of Murine Poxvirus-Specific CD8⁺ CTL Epitopes with Distinct Functional Profiles¹

Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655

Murine T cell epitopes against vaccinia virus (VV) have not been characterized to date in part due to the large and complex genome of VV. We have identified and characterized two CD8⁺ T cell epitopes on the A47L (modified VV Ankara strain (MVA)-029) and J6R (MVA-043) proteins of VV that are D^b and K^b restricted, respectively. Following i.p. immunization with VV New York City Board of Health (NYCBH) strain, MVA-029 peptide-stimulated splenocytes secreted IFN- from 7 days to 7 mo postimmunization, and virus-stimulated effectors were also able to lyse MVA-029-pulsed target cells at the same time points. In contrast, MVA-043 peptide-stimulated splenocytes secreted very low levels of IFN- only at day 7 but maintained the ability to lyse target cells up to 2 mo postimmunization. Both MVA-029 and MVA-043 peptide-stimulated lymph node cells degranulated similarly as assessed by Ag-induced CD107 expression. T cell responses to whole-virus stimulation remained robust and steady during the acute and memory T cell response to VV. Identification of T cell epitopes on VV will enable further studies to increase our understanding of the role of CD8⁺ T cells in VV infection and assist in the design of new protective strategies.

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